Development and content validation of a preliminary core set of patient- and caregiver-relevant outcomes for inclusion in a potential composite endpoint for Dravet Syndrome
Open accessAbstract
BACKGROUND: Dravet Syndrome (DS) is a rare developmental and epileptic encephalopathy characterized by multiple seizures, frequently prolonged and treatment refractory, with significant developmental disabilities and behavioral and psychiatric disorders. Patients with DS require intensive support and supervision from a caregiver, impacting significantly on both patients' and caregivers' lives. This study aimed to identify core concepts to measure the impact on both patients and caregivers in future DS clinical trials. METHODS: Qualitative concept elicitation interviews were conducted with caregivers and healthcare professionals involved in caring for children with DS (aged 2-18years) in France to identify important concepts related to the global impact of DS. Interviews explored a range of concepts, including triggers, symptoms, impacts, and coping strategies, from which a conceptual model was developed. A Delphi consensus panel with eight international clinical experts aimed to identify important and relevant endpoints. RESULTS: Seizure was the most commonly reported symptom with DS further impacting children's cognitive and behavioral functioning. Caregivers identified impact concepts not reported by healthcare professionals. Both groups described additional impacts on wider family members and home modifications. Clinical experts agreed on the inclusion of five patient- and caregiver-relevant concepts for measurement in future DS clinical trials in a composite endpoint. The five concepts for inclusion were; seizures, expressive communication of the child, receptive communication of the child, impact on daily activities, and social functioning of the caregiver. CONCLUSIONS: This study showed the wider potential impact of DS to extend beyond that of seizures, demonstrating that there is a need for additional patient- and caregiver-relevant concepts to be measured in clinical trials to fully identify the value of therapeutic interventions.
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The development of composite endpoints for DEE trials, acknowledging the importance of improving comorbidities as well as reducing seizure frequency, is a new area of trial design.
“The development of composite endpoints for DEE trials, acknowledging the importance of improving comorbidities as well as reducing seizure frequency, is a new area of trial design 225 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [225]
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- Authors
- Nabbout, R., Auvin, S., Chiron, C., Irwin, J., Mistry, A., Bonner, N., Williamson, N., & Bennett, B.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- Zogenix (United Kingdom) (GB)
- Adelphi Group (United Kingdom) (GB)
- Corresponding author
- Nabbout, Rima
- Irwin, John
- Mistry, Arun
- Bonner, Nicola
- Williamson, Nicola
- Bennett, Bryan
- Venue
- Epilepsy & Behavior
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 78
- Pages
- 232-242
- ISSN
- 1525-5050 (ISSN-L)
- OpenAlex
- W2766832340
- Cited by
- 80
- References
- 47
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 11 · 2019: 6 · 2018: 3
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Epilepsy & Behavior (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Zogenix International Ltd.
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Social Sciences › Sociology and Political Science › Delphi Technique in Research
- Social Sciences › Education › Health Education and Validation
- Keywords
- Dravet syndrome, developmental and epileptic encephalopathy, patient-reported outcomes, caregiver outcomes, composite endpoints, outcome measure development, concept elicitation, Delphi consensus, seizures, expressive communication, receptive communication, impact on daily activities, clinical trial endpoints
- MeSH terms
- Epileptic Syndromes, Adaptation, Psychological, Adolescent, Adult, Attitude of Health Personnel, Child, Developmental Disabilities, Child, Preschool, Communication, Concept Formation, Epilepsies, Myoclonic, Family, Female, France, Humans, Male, Middle Aged, Parent-Child Relations, Seizures, Spasms, Infantile, Caregivers, Outcome Assessment, Health Care
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